Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r²=0.98–1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml⁻¹ of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=−0.06, P-value=2.7 × 10⁻⁴). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections

Family Business Restructuring:A Review and Research Agenda

Although business restructuring occurs frequently and it is important for the prosperity of family firms across generations, research on family firms has largely evolved separately from research on business restructuring. This is a missed opportunity, since the two domains are complementary, and understanding the context, process, content, and outcome dimensions is relevant to both research streams. We address this by examining the intersection between research on business restructuring and family firms to improve our knowledge of each area and inform future research. To achieve this goal, we review and organize research across different dimensions to create an integrative framework. Building on current research, we focus on 88 studies at the intersection of family firm and business restructuring research to develop a model that identifies research needs and suggests directions for future research

Robots mobiles agiles pour les services environnementaux

International audienceAlthough the wheeled locomotion proved to be very efficient on smooth grounds, it still encounters great difficulties in natural environments, where the ground is subject to wide variations in term of geometry (irregular surface, presence of obstacles...) and material properties (cohesion, grip condition...). This chapter presents recent developments and original systems that allow to model and improve the capacities of wheeled mobile service robots on natural ground. First is considered the case of low speed motion. Section 2 presents recent results on reconfigurable suspensions that have two states and can decrease lateral friction and energy consumption during turns for skid-steering vehicles. Section 3 presents an original hybrid kinematics that combines wheels with an articulated frame for creating a mobile wheeled robot with high obstacle-climbing capacities, using only one supplemental actuator. Other advances deals with high speed motion. Section 4 describes a new device dedicated to vehicle dynamic stability, which improves lateral stability on fast mobile robots during turns and contributes to rollover prevention. Finally, Section 5 introduces innovative suspensions with two DOF for fast obstacle crossing. They damp vertical shocks, such as ordinary suspensions, but also horizontal ones, contributing to tip-over prevention on irregular grounds that feature many steep obstacles

Remote ischemic conditioning in septic shock (RECO-Sepsis): study protocol for a randomized controlled trial

BACKGROUND: Septic shock is a major public health problem that is associated with up to 50% mortality. Unfavorable outcomes are mainly attributed to multiple organ failure (MOF) resulting from an uncontrolled inflammatory response and ischemia-reperfusion processes. REmote ischemic COnditioning (RECO) is a promising intervention to prevent ischemia-reperfusion injury. We hypothesize that RECO would reduce the severity of septic shock-induced MOF. METHODS/DESIGN: RECO in septic shock patients (RECO-Sepsis study) is an ongoing, prospective, multicenter, randomized, open-label trial, testing whether RECO, as an adjuvant therapy to conventional treatment in septic shock, decreases the severity of MOF as assessed by the Sequential Organ Failure Assessment (SOFA) score. Adult patients admitted to an intensive care unit with documented or suspected infection, lactatemia \textgreater 2 mmol/l, and treated with norepinephrine for less than 12 h are potentially eligible for the study. Non-inclusion criteria are: having expressed the wish not to be resuscitated, contraindication for the use of a brachial cuff on both arms, intercurrent disease with an expected life expectancy of less than 24 h, cardiac arrest, and pregnant or breastfeeding women. After enrollment, patients are randomized (n = 180) 1:1 to receive RECO or no adjunctive intervention. RECO consists of four cycles of cuff inflation to 200 mmHg for 5 min and then deflation to 0 mmHg for another 5 min. RECO is performed at inclusion and repeated 12 and 24 h later. The primary endpoint is the mean daily SOFA score up to day 4 after inclusion. Secondary outcomes include the need for organ support, hospital length of stay, and 90-day mortality. DISCUSSION: Results of this proof-of-concept trial should provide information on the efficacy of RECO in patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov, ID: identifier: NCT03201575 . Registered on 28 June 2017

Cartesian Stiffness Matrix Mapping of a Translational Parallel Mechanism with Elastic Joints

This paper is devoted to calculating the Cartesian stiffness matrix of a translational parallel manipulator with elastic joints. The calculation takes into account the contribution of the Jacobian variation because of the change of manipulator configuration due to the elasticity and it covers the entire theoretical workspace of the manipulator. Three kineto-static adimensional indices are proposed to measure the response of the manipulator in terms of stiffness